2019 – 2021 – Molecular Mechanisms of Functional Phase Separation

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Microfluidic Analysis of Multicomponent Phase Separation in Ubiquitin-Dependent Proteostasis
Microfluidic Analysis of Multicomponent Phase Separation in Ubiquitin-Dependent Proteostasis
We develop microfluidic workflows to map enzymatic activity and compositional control of tumour suppressor SPOP with its substrates in liquid nuclear bodies. Various membraneless bodies that form through liquid phase […]
Role of Sub-Membranous Phase Separation in the Regulation of Myelin Membrane Structure and Function
Role of Sub-Membranous Phase Separation in the Regulation of Myelin Membrane Structure and Function
Mikael Simons +49 941-9437751 Institute of Neuronal Cell Biology (TUM-NCB)Technical University MunichGerman Center for Neurodegenerative Diseases (DZNE)Feodor-Lynen-Straße 1781377 Munich Office: +49 89 440046495 Lab: +49 89 440046479
Dissecting the Nuclear Pore-Like Permeability Barrier Function of Phase Separated Liquid FG Nucleoporin Condensates
Dissecting the Nuclear Pore-Like Permeability Barrier Function of Phase Separated Liquid FG Nucleoporin Condensates
The nuclear pore complex (NPC) is a ~120 MDa complex built from multiple copies of ~30 different nucleoporins (Nups). The NPC traverses the nuclear envelope and functions as “gatekeeper” for […]
Molecular Basis for the Central Role of the DEAD-Box Helicase Dhh1 in the Formation and Function of Processing Bodies
Molecular Basis for the Central Role of the DEAD-Box Helicase Dhh1 in the Formation and Function of Processing Bodies
Processing-bodies (P-bodies) contain the machinery that is involved in 5ʼ to 3ʼ mRNA degradation. This includes the DEAD box RNA helicase Dhh1 as well as the mRNA decapping enzyme Dcp2, […]
Dynamics and Buffering Functions of Nuclear Actin-Cofilin Assemblies in Cellular Stress Response
Dynamics and Buffering Functions of Nuclear Actin-Cofilin Assemblies in Cellular Stress Response
Actin is the most abundant protein in most eukaryotic cells and is well known for its capability to polymerize into dynamic filaments in the cytoplasm. Actin is now also recognized […]
Phase Separation driven Heterochromatin Formation as a Regulatory Mechanism for Repeat Silencing and Cellular Differentiation
Phase Separation driven Heterochromatin Formation as a Regulatory Mechanism for Repeat Silencing and Cellular Differentiation
Pericentric heterochromatin in mouse and Drosophila assembles via heterochromatin protein 1 (HP1) in a self-organizing manner into distinct nuclear subcompartments that are called chromocenters. During development chromocenters change their structure […]
Post-Translational Control of Gene Expression Noise by Liquid-Liquid Phase Separation
Post-Translational Control of Gene Expression Noise by Liquid-Liquid Phase Separation
Stochasticity in transcription and translation causes substantial cell-to-cell variability in protein concentrations across isogenic cells. A key question in biology is how cells manage to function robustly while their inner […]
Phase Separation of Membrane Scaffolding Proteins as a Mechanism to Control Formation of Tight Junctions
Phase Separation of Membrane Scaffolding Proteins as a Mechanism to Control Formation of Tight Junctions
In this project we aim to understand how tight junctions (TJ) assemble into a continuous sub-apical belt in epithelial cells. Based on cell biological and in vitro data we hypothesize […]
Active Microemulsification as a Principle of Chromatin Organization and its Role in Cell Fate Induction
Active Microemulsification as a Principle of Chromatin Organization and its Role in Cell Fate Induction
The cell nucleus displays a striking, widely conserved spatial compartmentalization. Inactive regions of the genome are sequestered to and compacted within a distinct comparment; active regions of the genome are […]
Molecular Mechanisms of Functionally Distinct Liquid-Liquid Phase Separation of Drosophila Loqs, Ago2 and dsRNA
Molecular Mechanisms of Functionally Distinct Liquid-Liquid Phase Separation of Drosophila Loqs, Ago2 and dsRNA
Small RNA silencing serves to regulate genes but also as a defense against pathogens and selfish genetic elements. In insects, a specialization of small RNAs and their biogenesis factors for […]
Conformational Selection in Liquid-Liquid Phase Separation: Integrating Protein Folding, Misfolding and Stress Granule Formation
Conformational Selection in Liquid-Liquid Phase Separation: Integrating Protein Folding, Misfolding and Stress Granule Formation
Intracellular membraneless organelles (MOs) form dynamically and thermodynamically reversible via liquid-liquid phase separation (LLPS). The molecular processes that drive MO formation are largely unknown, but recent deletion experiments showed that […]
Driving Forces of TDP-43 Phase Transitions and their Physiological and Pathological Consequences in Cells
Driving Forces of TDP-43 Phase Transitions and their Physiological and Pathological Consequences in Cells
Aberrant liquid-to-solid phase transitions of RNA-binding proteins (RBPs) with prion-like low complexity domains (LCD) are thought to underlie the formation of pathological RBP aggregates in a number of neurodegenerative diseases, […]
Phase Separation in PML Nuclear Bodies through a Multivalent PolySUMO-2/3 Network is required for Efficient DNA Recombination and Repair
Phase Separation in PML Nuclear Bodies through a Multivalent PolySUMO-2/3 Network is required for Efficient DNA Recombination and Repair
Membrane-less organelles in the nucleus of mammalian cells have been suggested recently to assemble and function via LLPS mechanisms. One main driver of LLPS at PML NBs appears to be […]
Phase Separation of Ki-67 during Mitotic Exit
Phase Separation of Ki-67 during Mitotic Exit
Recent studies have demonstrated that membrane-less condensates assemble by liquid-liquid phase separation of proteins that share multivalency, intrinsic disorder and low complexity sequences as common characteristics. The details of the […]
Molecular mechanisms of functional phase separation in eukaryotic gene transcription
Molecular mechanisms of functional phase separation in eukaryotic gene transcription
Transcription of protein-coding genes by RNA polymerase II (Pol II) is highly regulated during cell differentiation and organismal development. In human cells, Pol II transcription is regulated by ~1,600 transcription […]
The Formation of Phase-Separated Transcription Hubs and their Function in Transcription Regulation
The Formation of Phase-Separated Transcription Hubs and their Function in Transcription Regulation
Transcription hubs of transcription factors and RNA polymerase II have been observed in tissue culture cells and embryos. These transcription hubs are assembled through a phase separation mechanism driven by […]
Molecular and Cellular Determinants of Tau Protein Condensation into Dense Liquid Phases
Molecular and Cellular Determinants of Tau Protein Condensation into Dense Liquid Phases
The neuronal tau protein is involved in the regulation of the axonal microtubule skeleton in the brain. In neurodegenerative diseases such as Alzheimer’s disease (AD) and Frontotemporal dementia (FTD), tau […]
Development of a Combined Fluorescence, Optical Diffraction Tomography and Brillouin (FOB) Microscope for the Quantitative Investigation of Phase Transitions in Cells
Development of a Combined Fluorescence, Optical Diffraction Tomography and Brillouin (FOB) Microscope for the Quantitative Investigation of Phase Transitions in Cells
This project led by the Alberti and Guck teams will develop a new combined fluorescence, optical diffraction tomography and Brillouin (FOB) microscope and to use FOB microscopy to study physiological […]
Molecular mechanisms of physiological and aberrant phase transitions
Molecular mechanisms of physiological and aberrant phase transitions
The Alberti and Seidel teams will join forces to investigate the conformational dynamics of Fused in Sarcom (FUS) in vitro and in living cells using cutting-edge single molecule technology such […]